AB0499 LYMPHOID ORGANIZATION IN LUPUS NEPHRITIS: EVALUATING POSSIBLEAUTO ANTIGENS
Authors: V. A. Pacucci, F. R. Spinelli, C. Garufi, F. Ceccarelli, S. Colafrancesco, M. Leopizzi, C. Alessandri, F. Conti
Journal: Annals of the Rheumatic Diseases (2022)

Background Lupus nephritis (LN) represent one of the most frequent organ manifestations and one the major cause of morbidity in Systemic Lupus Erythematosus (SLE) patients. Tubule-interstitial infiltrate (TII) represents an independent prognostic factors of renal outcome 1 . Objectives The aim of the study was to evaluate the inflammatory infiltrates organization in kidney biopsies obtained from LN patients and to investigate possible autoantigens for in situ immune response. Methods Paraffin embedded kidney specimens collected since 2017 from SLE patients who underwent a renal biopsy for diagnostic purpose were re-evaluated 2 . Clinical, laboratory and histological data were collected in a standardized, computerized and electronically filled form, including demographics and past medical history. Disease activity was assessed by using SLEDAI-2K and remission in response to therapy was defined as a score 0 of renal item of the SLEDAI 3 . The cellular infiltrate were assessed by hematoxylin-eosin and by immunohistochemistry with a staining of sequential sections for monoclonal antibodies to CD3, CD20, CD21. Staining for detections of LL-37, vimentin and citrulline was made 4 . Serological levels of CXCL13 and anti-vimentin antibodies (AVAs) were evaluated in a subgroup of patients. Results Eighteen paraffin embedded renal specimens with TII, from LN patients were re-evaluated (F:M = 17:1, median age at biopsy-SD years 37-23; median disease duration at date of biopsy-IQR 3-4 years). A histo-morphologic grading score was performed based on the total count of TI lymphocytes and the presence of ectopic lymphoid structures-ELSs (grade 3-G3) (Figure 1). A correlation was found between G3 structures and the absence of renal remission with conventional immunosuppressive therapy (P=0.0026). Samples with G3 foci showed significantly higher intensity of LL37 (P=0.013) and LL37 co-localization (P=0.006) compared to the other lymphocytic infiltrates. No correlation was found among the intensity of vimentin and citrulline and the grade of lymphoid aggregates. A statistically significant inverse correlation between AVAs serum levels and response to therapy was found (P=0.0048). Moreover, higher level of AVAs and CXCL13 were found in patients with G3 structures. To note, two patients underwent anti-CD20 therapy but renal remission was achieved only in the patients displaying G3 structure. Figure 1. Conclusion The study demonstrated that tubule-interstitium involvement is associated with the presence of lymphoid aggregation and poor renal outcome. For the first time we demonstrated that patients with G3 structures had a significant decreased response to immunosuppressant conventional therapies compared to those without ELSs. These results suggest a possible phatogenetic, prognostic and therapeutical role of lymphocytic aggregates. In addiction, LL37, thus NETosis, could have a possible role in inducing the formation of lymphocytic structures. Moreover, patients with a G3 foci showed high serological levels of AVAs and CXCL13, thus, promoting their possible role as circulating biomarkers of the presence of ELSs. References [1]Bajema, I. M. et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 93,789–796 (2018). [2]Weening JJ et al. International Society of Nephrology Working Group on the Classification of Lupus Nephritis; Renal Pathology Society Working Group on the Classification of Lupus Nephritis. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb;65(2):521-30. [3]Gladman DD et al. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29:288-91. [4]Bombardieri M et al. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol. 2017 Mar;13(3):141-154. Disclosure of Interests None declared